US FDA Naming Guidance For Biologicals Likely To Change Again

The FDA's decision to again revise its naming guidance for all biologicals highlights the pressure the Agency is under from different parts of the pharmaceutical industry.

Crucially, the FDA's language is not distinguishing between originator and biosimilar products, but referring to all as biologicals; this is in part a preparation for the arrival of interchangeable biosimilars, anticipated in a year's time.

There remains no international consensus on naming conventions; it is likely therefore that this guidance will change again.

The FDA is again amending its guidance on naming conventions for biologics and biosimilars. In a statement released by FDA Commissioner Scott Gottlieb, the Agency noted that it was at a critical point for the future of biosimilars in the US, with millions of American patients poised to benefit from increased utilisation of biosimilars.

Gottlieb's statement noted that, since the biosimilar pathway was established in 2010, there has been a debate over how biological products should be named, and whether a unique identifier such as a distinguishing suffix should be added to the non-proprietary names of biological products to help ensure pharmacovigilance. Gottlieb commented that some have argued that the addition of a distinguishing suffix could serve as a barrier to the use of biosimilars and thus impact competition. Gottlieb responded by saying: 'We strongly believe in the ability of biosimilars to promote competition, lower prices and foster greater access. And we're fully committed to the suite of announced and upcoming policies to help advance the goal of a robust, high-quality, competitive market for biosimilar products. But I do not believe that the naming convention should be used to advance these goals if it could come at the expense of the ability to ensure patient safety. Nor do I believe the inclusion of a suffix will frustrate the broader aim of inspiring strong biosimilar competition.'

In January 2017, the FDA published a guidance document in which the Agency sought to balance these concerns by using a distinguishing suffix for both originator biologics and biosimilars. By applying the policy evenly, the FDA was seeking to advance the goal of patient safety, but without creating a misimpression that products with these suffixes were inferior to those without. In addition, the FDA announced in the January 2017 guidance that it was considering the process of retrospectively changing the names of biological products already on the market to include distinguishable suffixes.

However, in newly released guidance, the FDA has stated that it no longer intends to modify the non-proprietary names of biologics that have already been licensed or approved under the Public Health Services Act (PHSA) to include a suffix. Additionally, the Agency does not intend to apply the naming convention to the non-proprietary names of transition biological products. In the future, for interchangeable biosimilars, the FDA intends to designate a non-proprietary name that is a combination of the product's core name and a distinguishing suffix that is devoid of meaning and composed of four lowercase letters. This is the same as the system that was implemented after the January 2017 guidance; for example, in November 2018, the FDA approved Coherus Biosciences' Udenyca as a biosimilar version of Amgen's pegfilgrastim product, Neulasta. The FDA designated Udenyca's non-proprietary name as pegfilgrastim-cbqv.

Transition biological products are defined as those that are subject to an approved application under section 505 of the Federal Food, Drug and Cosmetic Act (FDCA) as of March 23 2020, when such an application will be deemed to be a BLA under section 351 of the PHSA. From March 2020, the approved marketing applications for a small subset of biological products such as insulin and human growth hormone, which are currently regulated under the FDCA, will be deemed to be biologics licensed under section 351 of the PHSA. This will open up a new range of product to competition and is a key part of the FDA's efforts to improve biosimilar competition in the US.

The FDA has argued that the changes with regard to naming conventions will help secure pharmacovigilance so that the Agency can effectively monitor all biologic products post-marketing, including originator and biosimilar products, and promote patient safety. To aid in adverse event report tracking, originator, biosimilar and interchangeable products will have non-proprietary names that are distinct from each other. Additionally, under this updated policy, any product that is first licensed as a biosimilar and later determined to be interchangeable will keep its non-proprietary name after receiving a determination of interchangeability.

The FDA added that this move will provide consistency amongst biologics and will help ensure healthcare providers and patients have confidence in the safety and efficacy of any biological product on the market, be it originator or biosimilar. The unique four-letter suffix that will be incorporated as part of a biological's non-proprietary name is being applied to originator products as well as biosimilar and interchangeable products, to ensure that all can be appropriately distinguished at the pharmacy level. The FDA stated that because biologics are generally complex and typically impossible to replicate in the way small-compound drugs can be, and even though biosimilars have no clinically meaningful differences from the reference product, these unique suffixes are a critical component of the Agency's ability to track adverse events to a specific biological product and manufacturer so that appropriate action can be taken when needed to protect patients.

The Agency stressed that the naming convention is primarily intended to ensure patient safety by helping providers and patients properly identify products where it is important to be able to distinguish between different medicines and different versions of similar or interchangeable products. The FDA noted that as it stands, the proper names of all 18 approved biosimilars have been approved with the four-letter suffixes, as have the proper names of 27 originator biological products. As the FDA continues to apply this policy, it expects that a steadily increasing proportion of licensed biological products, including originator products, will have non-proprietary names that include four-letter suffixes. Of the biological products within the scope of the policy, only those originator products licensed prior to the implementation of the policy will lack a suffix.

FDA-APPROVED BIOSIMILARS

Company

Biosimilar Brand Name

Non-Proprietary Name

Reference Product (Company)

Approval Date

Sandoz

Zarxio

Filgrastim-sndz

Neupogen (Amgen)

Mar-15

Celltrion/Hospira

Inflectra

Infliximab-dyyb

Remicade (Janssen Biotech)

Apr-16

Sandoz

Erelzi

Etanercept-szzs

Enbrel (Amgen)

Aug-16

Amgen

Amjevita

Adalimumab-atto

Humira (AbbVie)

Sep-16

Samsung Bioepis

Renflexis

Infliximab-abda

Remicade (Janssen Biotech)

May-17

Boehringer Ingelheim

Cyltezo

Adalimumab-adbm

Humira (AbbVie)

Aug-17

Amgen

Mvasi

Bevacizumab-awwb

Avastin (Roche)

Sep-17

Mylan

Ogivri

Trastuzumab-dkst

Herceptin (Roche)

Dec-17

Pfizer

Ixifi

Infliximab-qbtx

Remicade (Janssen Biotech)

Dec-17

Hospira (Pfizer)

Retacrit

Epoetin alfa-epxb

Epogen/Procrit (Amgen)

May-18

Mylan

Fulphila

Pegfilgrastim-jmdb

Neulasta (Amgen)

Jun-18

Pfizer

Nivestym

Filgrastim-aafi

Neupogen (Amgen)

Jul-18

Sandoz

Hyrimoz

Adalimumab-adaz

Humira (AbbVie)

Oct-18

Coherus Biosciences

Udenyca

Pegfilgrastim-cbqv

Neulasta (Amgen)

Nov-18

Celltrion/Teva Pharmaceutical Industries

Truxima

Rituximab-abbs

Rituxan (Roche)

Nov-18

Celltrion/Teva Pharmaceutical Industries

Herzuma

Trastuzumab-pkrb

Herceptin (Roche)

Dec-18

Samsung Bioepis

Ontruzant

Trastuzumab-dttb

Herceptin (Roche)

Jan-19

Pfizer

Trazimera

Trastuzumab-qyyp

Herceptin (Roche)

Mar-19

Note: Complete as at March 18 2019. Source: US FDA, Fitch Solutions

The FDA is responding to concerns that were raised after the Agency issued its 2017 guidance. Stakeholders raised the concern that changing the names of older biologics to add suffixes would impose costs on the healthcare system and had the potential to create confusion that could increase risks to patients as drug names do not often change once they have gone on the market. The FDA responded that it had determined that the public health goals of the naming policy could still be accomplished by applying the naming convention to newly licensed biological products, while avoiding the negative consequences raised by extending the naming convention to previously licensed products. The Agency argued that to go back and change the names of already approved products would be costly to the healthcare system; if those costs were to be passed on to patients, the impact would run directly counter to the goals of access and affordability that underlie the biosimilars programme. Moreover, requiring retrospective names changes would not help advance the interest of effective pharmacovigilance since these products are already generally distinguishable by their proper names. Consequently, the FDA concluded that it would not require these legacy names to be changed.

The Agency stated that in advancing consistency in the naming convention for all newly licensed biologicals, including originator, biosimilar, and in time interchangeable, it aims to mitigate the risk of false perceptions from healthcare providers and patients that there is a difference in the relative safety and effectiveness of these biological products based on their name. The FDA added that it expects that as time progresses and more biologicals are introduced to the market with distinguishable suffixes, patients and providers increasingly will understand that the suffixes reflect a consistent naming convention and are not an indicator of product quality.

The new guidance will also attract criticism. The Association for Affordable Medicines (AAM), the industry body that represents generic and biosimilar companies, commented that it was reviewing the guidance and will submit comments to the guidance's docket. The AAM added however that the current requirement of suffixes 'presents a significant, artificial barrier to biosimilars that is misaligned with the Agency's own Biosimilars Action Plan and the Trump administration's commitment to lowering drug prices for America's patients.' From this, it is likely that the AAM will continue to oppose the use of suffixes.

The Biosimilars Forum was more forceful in its criticism. The Forum describes itself as representing the majority of companies with the most significant US biosimilar development portfolios. Members are both traditionally innovative and generic companies, and include Boehringer Ingelheim, Coherus BioSciences, Pfizer, Samsung Bioepis, Sandoz (Novartis) and Teva Pharmaceutical Industries.

Responding to the new draft guidance, the Forum stated that the announcement 'is a direct blow to biosimilars uptake in the US.' The organisation added that 'The decision abandons the retrospective addition of a suffix to origination biologics, leading to an unsubstantiated notion that strict pharmacovigilance is only essential for biosimilars. This decision will disincentivise biosimilar uptake at a time when the Government should be implementing policies that incentivise the use of biosimilars...'

Naming conventions for biologicals is an issue that has proved to be difficult to resolve. Whilst patient safety is one aspect of the issue, critics have long argued that an ulterior motive amongst companies and organisations pushing for introducing different non-proprietary names for originator and biosimilar products has been to raise doubts over the safety of biosimilars, a view that has now been repeated by the Biosimilars Forum. The original FDA guidance did create a level playing field, requiring all biologicals to include a four-letter suffix. The new guidance will in time likely encompass nearly all biologicals, as the older products without suffixes are eventually phased out, but it is likely that criticism of the change in approach will grow.

A second issue will be international conventions. At the moment there is a lack of international consensus on the issue of biological naming. For example, in the EU, international non-proprietary names are used unmodified, and supported by 2D-barcoding. In Japan, the 'BSn' biosimilar identifier is used. The World Health Organization has proposed using a Biological Qualifier in connection with the international non-proprietary name. This is similar to the FDA's suffixes; however, this remains under review. From a cost perspective, companies are increasingly likely to push for an international universally recognised system; this could result in further changes to the FDA's guidance.